Transcript
AAIC 2026 Eisai
[00:00:00]
Intro: Welcome to NeuroFrontiers, a series in which Practical Neurology partners with ReachMD to bring you clinical research and advances that support clinicians in diagnosing and treating neurologic conditions. In this episode, Dr. Michael Irizarry discusses subcutaneous lecanemab for early Alzheimer disease, including the evidence supporting its use, safety monitoring, patient selection, and considerations for at-home administration.
This is Joe Rusko, the editor-in-chief of Practical Neurology, and i'm here with Dr. Irizarry. Dr. Irizarry, please introduce yourself and tell us a little bit - about your role at Eisai.
Thank you. It's a pleasure to be speaking with you. I'm a neurologist, and I lead clinical development for the neurology portfolio at Eisai. and I've been working on Alzheimer's research for over 30 years, starting out at Mass General Hospital and Harvard, and then [00:01:00] through the pharmaceutical industry as well.
And I've been at Eisai now the past seven years. Thank you. So everyone is really excited at the AIC 2026 meeting about the subcutaneous version of Leqembi being approved for initiation dose. but I know our audience is gonna ask, what is the evidence supporting that decision from the FDA?
We're also just extremely excited that now patients have another option for how to administer lecanemab for early Alzheimer's disease. and the evidence base for it really builds on the entire development program of lecanemab. So from our phase two study, we explored a range of doses to understand the dose response with regards to amyloid clearance and efficacy on slowing clinical decline.
And then we had this large phase three [00:02:00] program that further confirmed the efficacy and the relationship of biomarkers to that outcome. So building on those studies that led to the approval of IV lecanemab, we added a subcutaneous development program that helped us understand what drove efficacy, what drove amyloid reduction was the levels of lecanemab in the blood, what we call the exposure of lecanemab.
And we showed that if you have the same exposure, the same average blood levels for IV or subq, you have the same amount of amyloid clearance, and the expectation would be the same amount of efficacy and the same safety with regards to amyloid-related imaging abnormalities. so our subcutaneous program showed that [00:03:00] amyloid reduction was exposure-related, and so all we had to do was find that subcutaneous dose that matched the exposure in the blood of the IV dose.
And we confirmed that 500 milligram administered in two shots by auto-injector weekly matched the exposure of the IV dose given every two weeks.
So how does changing the route of administration change how neurologists should think about safety monitoring? So the safety profile of the intravenous formulation and the subcutaneous formulation is the same with regards to amyloid-related imaging abnormalities. a adverse event that's associated with these anti-amyloid treatments are amyloid-related imaging [00:04:00] abnormalities or ARIA. There are two types. One is ARIA edema, which is increased fluid in the brain, or ARIA hemosiderin, which are small areas of bleeding in the brain. And these are believed to occur because these treatments clear the amyloid that's around blood vessels, and those blood vessels become leaky.
Though those adverse events are typically asymptomatic, they're identified by MRI, but rarely they can be symptomatic or fatal. the important thing for both IV and subQ is first, to discuss these adverse events with people that may be eligible for treatment, to do an MRI and an APOE genotype to identify their risk for these abnormalities.
So for instance, people that carry two APOE4 alleles as their genotype have an increased risk , or [00:05:00] people that have evidence of already, areas of bleeding in the brain have a higher risk and then, with treatment during the first six months, there are four MRI scans that are performed to try to identify these early.
And if they occur, then the treatment can be paused and then resumed once, they recover. So those aspects are the same between IV and subQ, and the monitoring and management of ARIA is the same for both. The safety difference is related to infusion-related reactions. So in our clinical trials for IV, with the first dose of IV, about a quarter of patients developed infusion-related reactions.
And that's typically flu-like symptoms with the first dose that typically resolve over a few hours,
We see much less of that with the subcutaneous formulation. For most [00:06:00] of our studies, maybe about 2% to 3% , of people might have mild flu-like symptoms after getting the subcutaneous injection. So that allows people to, be in-injected- With supervision over the first, two doses,, and then be able to administer at home, afterwards, so they don't need the monitoring after an infusion.
People do get, local injection site reactions, so redness or swelling, and that's on the order , of 10% of people, maybe as high as 17% in, the different studies that, we did. , In the label, it, does require that people can identify if they're having these types of reactions, these, , more severe reactions, before being considered for subcutaneous treatment.
The two criteria for subcutaneous treatment is, one, being able to administer it and follow the instructions for use , by the patient or by the care partner, [00:07:00] and then also be able to recognize if there are any serious side effects from the injection. Thank you. , So speaking of patients, which are most appropriate for subcu initiation?
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In the US, , anybody who's eligible for IV lecanemab- Mm is eligible for subcutaneous lecanemab , as an option. , The only criteria is that , , either the patient who's self-administering or a care partner that may be administering to a patient, , can follow the instructions for use and can perform the injection.
And then the second criteria is that they can identify if there are any serious side effects from it. The physician should reassess over time whether that continues to be the case. We've done a series of studies called human factor studies, which tests the ability of patients or care partners to follow the instructions for use and to be able to give [00:08:00] injections.
And across either mild cognitive impairment or mild dementia or younger patients and older patients, we didn't see any real differences in the ability to, self-administer or have a care partner administer, with appropriate training. So, I think this is an option for any patient that is eligible for lecanemab treatment.
Eisai is, setting up a range of resources to be able to support, clinicians, patients, care partners in terms of, understanding how to administer the injection, how to monitor the injection.
There is information at Leqembi.com, that can provide additional resources. And certainly if there's any concerns that the patient or care partner have, they should contact their clinician, , to address those
Any other, insights ? Well, we've had the experience of the [00:09:00] subcutaneous maintenance dosing. So a- after 18 months of IV biweekly dosing, and now after 18 months of the 500 milligram subcutaneous initiation dose, there is the option to transition to maintenance dosing.
The maintenance dose for subcutaneous is 360 milligrams. It's a single injection weekly. There's also a maintenance dose for IV that's a single dose monthly. And we've presented some data in terms of patient satisfaction, care partner satisfaction, and the availability of this option seems to be highly favored , by people , who have tried it and who have initiated it.
It does make it easier because people don't have to go to infusion centers to get IV dosing, and that when you consider the transportation, the one-hour infusion, the monitoring afterwards, that, can be a considerable effort I [00:10:00] will say, though, that, in clinical studies, some patients do prefer IV. The more frequent touch points- with, the infusion centers or their physicians.
The way that it's set up, some people like the social interaction that goes with that. , We're very excited to have both of these options available.
So we do have support services in terms of providing information and navigators that can help patients and families particularly, understand insurance coverage and also help physicians with that.
This is really an exciting time for, for Alzheimer's disease research and treatment. , We're seeing, really remarkable change in the way the disease is diagnosed and with the opportunities for treatment.
Well, thank you for your time and insights today.
My pleasure. Thank you so much.
Outro: Thank you, doctor, for sharing your insights in this episode of Neuro Frontiers, and thank you to our listeners. NeuroFrontiers is presented by the editors [00:11:00] of Practical Neurology. Visit PracticalNeurology.com for more podcasts covering the field of neurology.
